Guanfacine: uses, appearance and warnings

Guanfacine extended-release tablets are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications [see Clinical Studies (14)] . Guanfacine extended-release tablets are a central alpha 2A -adrenergic receptor agonist indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications (1, 14).

1 mg, 2 mg, 3 mg and 4 mg extended-release tablets Extended-release tablets: 1 mg, 2 mg, 3 mg and 4 mg (3)

Guanfacine extended-release tablets, USP are supplied in 1 mg, 2 mg, 3 mg, and 4 mg strength as follows: Guanfacine extended-release tablets, USP 1 mg are white to off-white, round shaped tablets with “ RJ70 ” debossed on one side and plain on the other side. NDC 63304-924-30 Bottles of 30 NDC 63304-924-01 Bottles of 100 NDC 63304-924-05 Bottles of 500 Guanfacine extended-release tablets, USP 2 mg are white to off-white, oval-shaped tablets with “ RJ71 ” debossed on one side and plain on the other side. NDC 63304-925-30 Bottles of 30 NDC 63304-925-01 Bottles of 100 NDC 63304-925-05 Bottles of 500 Guanfacine extended-release tablets, USP 3 mg are green colored, round shaped tablets with “ RJ72 ” debossed on one side and plain on the other side. NDC 63304-926-30 Bottles of 30 NDC 63304-926-01 Bottles of 100 NDC 63304-926-05 Bottles of 500 Guanfacine extended-release tablets, USP 4 mg are green colored, oval-shaped tablets with “ RJ73 ” debossed on one side and plain on the other side. NDC 63304-927-30 Bottles of 30 NDC 63304-927-01 Bottles of 100 NDC 63304-927-05 Bottles of 500 Storage - Store at 20° - 25° C (68° - 77° F) [See USP Controlled Room Temperature].

Guanfacine is contraindicated in patients with a history of a hypersensitivity reaction to guanfacine extended-release tablets or its inactive ingredients, or other products containing guanfacine. Rash and pruritus have been reported. History of hypersensitivity to guanfacine, its inactive ingredients, or other products containing guanfacine (4).

Hypotension, bradycardia, syncope: Titrate slowly and monitor vital signs frequently in patients at risk for hypotension, heart block, bradycardia, syncope, cardiovascular disease, vascular disease, cerebrovascular disease or chronic renal failure. Measure heart rate and blood pressure prior to initiation of therapy, following dose increases, and periodically while on therapy. Avoid concomitant use of drugs with additive effects unless clinically indicated. Advise patients to avoid becoming dehydrated or overheated (5.1). Sedation and somnolence: Occur commonly with guanfacine. Consider the potential for additive sedative effects with CNS depressant drugs. Caution patients against operating heavy equipment or driving until they know how they respond to guanfacine (5.2). Cardiac Conduction Abnormalities: May worsen sinus node dysfunction and atrioventricular (AV) block, especially in patients taking other sympatholytic drugs. Titrate slowly and monitor vital signs frequently (5.3). Rebound Hypertension: Abrupt discontinuation of guanfacine can lead to clinically significant and persistent rebound hypertension. Subsequent hypertensive encephalopathy was also reported. To minimize the risk of rebound hypertension upon discontinuation, the total daily dose of guanfacine should be tapered in decrements of no more than 1 mg every 3 to 7 days (5.4). 5.1 Hypotension, Bradycardia, and Syncope Treatment with guanfacine extended-release tablets can cause dose-dependent decreases in blood pressure and heart rate. Decreases were less pronounced over time of treatment. Orthostatic hypotension and syncope have been reported [see Adverse Reactions (6.1)] . Measure heart rate and blood pressure prior to initiation of therapy, following dose increases, and periodically while on therapy. Titrate guanfacine slowly in patients with a history of hypotension, and those with underlying conditions that may be worsened by hypotension and bradycardia; e.g., heart block, bradycardia, cardiovascular disease, vascular disease, cerebrovascular disease, or chronic renal failure. In patients who have a history of syncope or may have a condition that predisposes them to syncope, such as hypotension, orthostatic hypotension, bradycardia, or dehydration, advise patients to avoid becoming dehydrated or overheated. Monitor blood pressure and heart rate, and adjust dosages accordingly in patients treated concomitantly with antihypertensives or other drugs that can reduce blood pressure or heart rate or increase the risk of syncope. 5.2 Sedation and Somnolence Somnolence and sedation were commonly reported adverse reactions in clinical studies [see Adverse Reactions (6.1)] . Before using guanfacine extended-release tablets with other centrally active depressants, consider the potential for additive sedative effects. Caution patients against operating heavy equipment or driving until they know how they respond to treatment with guanfacine extended-release tablets . Advise patients to avoid use with alcohol. 5.3 Cardiac Conduction Abnormalities The sympatholytic action of guanfacine may worsen sinus node dysfunction and atrioventricular (AV) block, especially in patients taking other sympatholytic drugs. Titrate guanfacine slowly and monitor vital signs frequently in patients with cardiac conduction abnormalities or patients concomitantly treated with other sympatholytic drugs. 5.4 Rebound Hypertension In post marketing experience, abrupt discontinuation of guanfacine extended-release tablets has resulted in clinically significant and persistent rebound hypertension above baseline levels and increases in heart rate. Hypertensive encephalopathy has also been reported in association with rebound hypertension with both guanfacine extended-release and immediate release guanfacine [see Adverse Reactions (6.2)] . In these cases, high-dosage guanfacine was discontinued; concomitant stimulant use was also reported, which may potentially increase hypertensive response upon abrupt discontinuation of guanfacine extended-release tablets. Children commonly have gastrointestinal illnesses that lead to vomiting, and a resulting inability to take medications, so they may be especially at risk for rebound hypertension. To minimize the risk of rebound hypertension upon discontinuation, the total daily dose of guanfacine should be tapered in decrements of no more than 1 mg every 3 to 7 days [see Dosage and Administration (2.5)] . Blood pressure and heart rate should be monitored when reducing the dose or discontinuing guanfacine extended-release tablets. If abrupt discontinuation occurs (especially with concomitant stimulant use), patients should be closely followed for rebound hypertension.

The following serious adverse reactions are described elsewhere in the labeling: Hypotension, bradycardia, and syncope [see Warnings and Precautions (5.1)] Sedation and somnolence [see Warnings and Precautions (5.2)] Cardiac conduction abnormalities [see Warnings and Precautions (5.3)] Rebound Hypertension [see Warnings and Precautions (5.4)] Most common adverse reactions (≥ 5% and at least twice placebo rate) in fixed-dose monotherapy ADHD trials in children and adolescents (6 to 17 years): hypotension, somnolence, fatigue, nausea, and lethargy (6.1). Flexible dose-optimization ADHD trials in children (6 to 12 years) and adolescents (13 to 17 years): somnolence, hypotension, abdominal pain, insomnia, fatigue, dizziness, dry mouth, irritability, nausea, vomiting, and bradycardia (6.1). …

Table 14 contains clinically important drug interactions with guanfacine [see Clinical Pharmacology (12.3)] . Table 14: Clinically Important Drug Interactions: Effect of other Drugs on Guanfacine Concomitant Drug Name or Drug Class Clinical Rationale and Magnitude of Drug Interaction Clinical Recommendation Strong and moderate CYP3A4 inhibitors, e.g., ketoconazole, fluconazole Guanfacine is primarily metabolized by CYP3A4 and its plasma concentrations can be significantly affected resulting in an increase in exposure Consider dose reduction [see Dosage and administration (2.7)] Strong and moderate CYP3A4 inducers, e.g., rifampin, efavirenz Guanfacine is primarily metabolized by CYP3A4 and its plasma concentrations can be significantly affected resulting in a decrease in exposure Consider dose increase [see Dosage and administration (2.7)] Strong and moderate CYP3A4 inhibitors increase gu …